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Signaling cascades transmit information downstream and upstream but unlikely simultaneously
Simona Catozzi1, Juan Pablo Di-Bella2, Alejandra C Ventura2
1Université Côte d'Azur, CNRS, INLN, 1361 route des lucioles, Valbonne, 06560, France.
BMC Systems Biology
|August 27, 2016
Summary
Biochemical parameters control signal direction in cellular cascades. This study identifies conditions favoring forward or retro-signaling, revealing when retroactivity can be neglected and when cascades act as retro-signaling devices.
Area of Science:
- Cellular biology
- Biochemistry
- Systems biology
Background:
- Signal transduction enables cells to communicate with their environment.
- Signaling cascades transmit biochemical information intracellularly.
- Retroactivity allows perturbations to propagate upstream in cascades.
Purpose of the Study:
- To compare conditions favoring forward versus retro-signaling in cellular cascades.
- To elucidate the role of biochemical parameters in directing signal propagation.
- To identify specific parameter sets that enhance forward or retro-signaling regimes.
Main Methods:
- Mathematical analysis of cascade steady states using iterative maps.
- Numerical and statistical approaches on a 3-tier signaling cascade model.
- Random parameter scanning to compute the likelihood of signaling regimes.
Main Results:
- Cascade steady states are governed by second-order iterative maps, coupling tiers three-by-three.
- Biochemical parameters like kinetic rates and concentrations dictate signal direction.
- Identified conditions that specifically enhance forward or retro-signaling.
Conclusions:
- Parameter sets favoring forward and retro-signaling are generally opposed.
- Retroactive effects are often negligible in efficient forward-signaling cascades.
- Cascades can function as retro-signaling devices in specific, less-explored parameter spaces.
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